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Protein

Laforin

Gene

EPM2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Plays an important role in preventing glycogen hyperphosphorylation and the formation of insoluble aggregates, via its activity as glycogen phosphatase, and by promoting the ubiquitination of proteins involved in glycogen metabolism via its interaction with the E3 ubiquitin ligase NHLRC1/malin. Shows strong phosphatase activity towards complex carbohydrates in vitro, avoiding glycogen hyperphosphorylation which is associated with reduced branching and formation of insoluble aggregates (PubMed:16901901, PubMed:23922729, PubMed:26231210, PubMed:25538239, PubMed:25544560). Dephosphorylates phosphotyrosine and synthetic substrates, such as para-nitrophenylphosphate (pNPP), and has low activity with phosphoserine and phosphothreonine substrates (in vitro) (PubMed:11001928, PubMed:11220751, PubMed:11739371, PubMed:14532330, PubMed:16971387, PubMed:18617530, PubMed:22036712, PubMed:23922729, PubMed:14722920). Has been shown to dephosphorylate MAPT (By similarity). Forms a complex with NHLRC1/malin and HSP70, which suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system (UPS). Acts as a scaffold protein to facilitate PPP1R3C/PTG ubiquitination by NHLRC1/malin (PubMed:23922729). Also promotes proteasome-independent protein degradation through the macroautophagy pathway (PubMed:20453062).By similarity17 Publications
Isoform 2: does not bind to glycogen (PubMed:18617530). Lacks phosphatase activity and might function as a dominant-negative regulator for the phosphatase activity of isoform 1 and isoform 7 (PubMed:18617530, PubMed:22036712).2 Publications
Isoform 7: has phosphatase activity (in vitro).1 Publication

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.PROSITE-ProRule annotation2 Publications
[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei32SubstrateCombined sources1 Publication1
Binding sitei87SubstrateCombined sources1 Publication1
Binding sitei197SubstrateCombined sources1 Publication1
Binding sitei235SubstrateCombined sources1 Publication1
Binding sitei241SubstrateCombined sources1 Publication1
Active sitei266Phosphocysteine intermediatePROSITE-ProRule annotation6 Publications1
Binding sitei304SubstrateCombined sources1 Publication1
Sitei329Required for homodimerization1 Publication1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protein phosphatase
Biological processAutophagy, Carbohydrate metabolism, Glycogen metabolism

Enzyme and pathway databases

BRENDAi3.1.3.16 2681
ReactomeiR-HSA-3322077 Glycogen synthesis
R-HSA-3785653 Myoclonic epilepsy of Lafora
SIGNORiO95278

Protein family/group databases

CAZyiCBM20 Carbohydrate-Binding Module Family 20

Names & Taxonomyi

Protein namesi
Recommended name:
Laforin1 Publication (EC:3.1.3.-5 Publications, EC:3.1.3.161 Publication, EC:3.1.3.482 Publications)
Alternative name(s):
Glucan phosphatase2 Publications
Glycogen phosphatase2 Publications
Lafora PTPase
Short name:
LAFPTPase1 Publication
Gene namesi
Name:EPM2A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000112425.13
HGNCiHGNC:3413 EPM2A
MIMi607566 gene
neXtProtiNX_O95278

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Epilepsy, progressive myoclonic 2 (EPM2)14 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive and severe form of adolescent-onset progressive epilepsy. Typically, as seizures increase in frequency, cognitive function declines towards dementia, and affected individuals die usually within 10 years after onset. EPM2 occurs worldwide, but it is particularly common in the mediterranean countries of southern Europe and northern Africa, in southern India and in the Middle East. At the cellular level, it is characterized by accumulation of starch-like polyglucosans called Lafora bodies (LBs) that are most abundant in organs with the highest glucose metabolism: brain, heart, liver and skeletal muscle. Among other conditions involving polyglucosans, EPM2 is unique in that the inclusions are in neuronal dendrites but not axons and the forming polyglucosan fibrils are associated with the endoplasmic reticulum.
See also OMIM:254780
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01946525S → P in EPM2; atypical form; does not affect glycogen binding. 2 Publications1
Natural variantiVAR_01946628E → K in EPM2; does not affect glycogen binding. 1 Publication1
Natural variantiVAR_01946732W → G in EPM2; impairs protein stability; affects phosphatase activity; abolishes glycogen binding; abolishes phosphatase activity with insoluble glucan; disrupts the interaction with PPP1R3C. 6 PublicationsCorresponds to variant dbSNP:rs104893955EnsemblClinVar.1
Natural variantiVAR_01946984F → L in EPM2; affects phosphatase activity and glycogen binding; disrupts the interaction with PPP1R3C. 2 PublicationsCorresponds to variant dbSNP:rs1362231306Ensembl.1
Natural variantiVAR_01947088F → L in EPM2; does not affect glycogen binding. 1 Publication1
Natural variantiVAR_01947191R → P in EPM2; atypical form; learning difficuties with childhood-onset. 2 Publications1
Natural variantiVAR_019472108R → C in EPM2; loss of phosphatase activity; reduced self-interaction capacity; disrupts the interaction with PPP1R3C. 3 PublicationsCorresponds to variant dbSNP:rs137852915EnsemblClinVar.1
Natural variantiVAR_046383140K → N in EPM2. 1 Publication1
Natural variantiVAR_046384148N → Y in EPM2. 1 Publication1
Natural variantiVAR_019474171R → H in EPM2; results in ubiquitin-positive perinuclear aggregates; no effect on glycogen binding; abolishes phosphatase activity; may affect proper folding. 5 PublicationsCorresponds to variant dbSNP:rs137852916EnsemblClinVar.1
Natural variantiVAR_019475187T → A in EPM2; abolishes interaction with NHLRC1. 1 Publication1
Natural variantiVAR_019476194T → I in EPM2; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; reduced self-interaction capacity; abolishes interaction with NHLRC1, PPP1R3C and PRKAA2; no effect on phosphorylation of protein. 3 PublicationsCorresponds to variant dbSNP:rs375544596Ensembl.1
Natural variantiVAR_046385210E → K in EPM2. 1 Publication1
Natural variantiVAR_019477240G → S in EPM2; impaired phosphatase activity; does not affect glycogen binding; disrupts the interaction with PPP1R3C. 3 Publications1
Natural variantiVAR_019478279G → S in EPM2; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 5 PublicationsCorresponds to variant dbSNP:rs137852917EnsemblClinVar.1
Natural variantiVAR_019479293Q → L in EPM2; results in ubiquitin-positive perinuclear aggregates; may affect proper folding; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 4 PublicationsCorresponds to variant dbSNP:rs796052427EnsemblClinVar.1
Natural variantiVAR_019480294Y → N in EPM2; results in ubiquitin-positive perinuclear aggregates; impairs phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 4 Publications1
Natural variantiVAR_019481301P → L in EPM2; impairs protein stability; impairs phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 3 PublicationsCorresponds to variant dbSNP:rs796052428Ensembl.1
Natural variantiVAR_046386310L → W in EPM2; causes location of isoform 1 at cytoplasmic punctae; does not affect homodimerization of isoform 1 but prevents heterodimerization of isoform 1 and isoform 2. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi8V → A: Loss of phosphatase activity. No effect on glycogen binding. 1 Publication1
Mutagenesisi25S → A: Partial loss of phosphatase activity. Abolishes homodimerization. Abolishes interaction with NHLRC1, PPP1R3C and PRKAA2. Does not affect glycogen binding. Reduces stability of the protein. 1 Publication1
Mutagenesisi25S → D: Partial loss of phosphatase activity. Increases interaction with NHLRC1. Does not affect interaction with NHLRC1, PPP1R3C or PRKAA2. Does not affect binding to carbohydrate. Does not affect homodimerization. 1 Publication1
Mutagenesisi87K → A: Loss of phosphatase activity. Abolishes glycogen binding. 2 Publications1
Mutagenesisi99W → A: Strongly reduces phosphatase activity. Strongly reduces glycogen binding. 1 Publication1
Mutagenesisi109 – 110CC → SS: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity. 1 Publication2
Mutagenesisi123C → S: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity. 1 Publication1
Mutagenesisi126I → T: Strongly decreased phosphatase activity. No effect on glycogen binding. 1 Publication1
Mutagenesisi142T → A: Strongly decreased phosphatase activity. No effect on glycogen binding. 1 Publication1
Mutagenesisi168S → A or D: Abolishes interaction with NHLRC1. 1 Publication1
Mutagenesisi169C → S: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity. 1 Publication1
Mutagenesisi169C → S: No effect on phosphatase activity. 1 Publication1
Mutagenesisi171R → A: No effect on phosphatase activity. 1 Publication1
Mutagenesisi187T → D: Abolishes interaction with NHLRC1. 1 Publication1
Mutagenesisi194T → D: Does not affect interaction with NHLRC1, PPP1R3C or PRKAA2. 1 Publication1
Mutagenesisi197D → A: Strongly decreased phosphatase activity. No effect on glycogen binding. 2 Publications1
Mutagenesisi205C → S: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity. 1 Publication1
Mutagenesisi235D → A: Complete loss of phosphatase activity. Does not affect glycogen binding. 2 Publications1
Mutagenesisi236M → A: Complete loss of phosphatase activity. No effect on glycogen binding. 1 Publication1
Mutagenesisi250C → S: No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity. 1 Publication1
Mutagenesisi251L → A: Impairs protein stability. Strongly reduces phosphatase activity. No effect on glycogen binding. 1 Publication1
Mutagenesisi266C → S: Complete loss of phosphatase activity. Does not affect glycogen binding. Does not affect self-interaction. Increases the interaction with PPP1R3C. 7 Publications1
Mutagenesisi272R → A: Complete loss of phosphatase activity. 1 Publication1
Mutagenesisi321F → S: Impairs protein stability. Strongly reduces phosphatase activity. No effect on glycogen binding. 1 Publication1
Mutagenesisi329 – 331Missing : Fails to homodimerize. Does not affect carbohydrate binding or phosphatase activity. 1 Publication3
Mutagenesisi329C → S: Fails to homodimerize. Does not affect carbohydrate binding, interaction with NHLRC1, phosphatase activity, or ubiquitination by NHLRC1. 1 Publication1
Mutagenesisi329C → S: No effect on homodimerization. 1 Publication1

Keywords - Diseasei

Disease mutation, Epilepsy, Glycogen storage disease

Organism-specific databases

DisGeNETi7957
GeneReviewsiEPM2A
MalaCardsiEPM2A
MIMi254780 phenotype
OpenTargetsiENSG00000112425
Orphaneti501 Lafora disease
PharmGKBiPA27832

Chemistry databases

ChEMBLiCHEMBL2311242

Polymorphism and mutation databases

BioMutaiRNF213

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000948381 – 331LaforinAdd BLAST331

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei25Phosphoserine; by AMPK1 Publication1

Post-translational modificationi

Polyubiquitinated by NHLRC1/malin.1 Publication
Phosphorylation on Ser-25 by AMPK affects the phosphatase activity of the enzyme and its ability to homodimerize and interact with NHLRC1, PPP1R3C or PRKAA2.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO95278
PaxDbiO95278
PeptideAtlasiO95278
PRIDEiO95278
ProteomicsDBi50779
50780 [O95278-2]
50782 [O95278-4]
50783 [O95278-5]
50784 [O95278-6]
50785 [O95278-7]
50786 [O95278-8]

PTM databases

DEPODiO95278
iPTMnetiO95278
PhosphoSitePlusiO95278

Expressioni

Tissue specificityi

Expressed in heart, skeletal muscle, kidney, pancreas and brain. Isoform 4 is also expressed in the placenta.2 Publications

Gene expression databases

BgeeiENSG00000112425 Expressed in 222 organ(s), highest expression level in skeletal muscle tissue of rectus abdominis
CleanExiHS_EPM2A
ExpressionAtlasiO95278 baseline and differential
GenevisibleiO95278 HS

Organism-specific databases

HPAiHPA053643
HPA055468

Interactioni

Subunit structurei

Homodimer (PubMed:16971387, PubMed:18617530, PubMed:23922729, PubMed:25538239, PubMed:25544560). Interacts with itself (PubMed:14532330). Interacts with PPP1R3B, PPP1R3C, PPP1R3D, HIRIP5, and EPM2AIP1 (PubMed:12782127, PubMed:12915448, PubMed:14532330, PubMed:16901901, PubMed:18070875). Binds glycogen and Lafora bodies (PubMed:11739371, PubMed:14532330, PubMed:14706656, PubMed:15102711, PubMed:18617530, PubMed:22036712). Interacts with NHLRC1/malin (via the NHL repeats) (PubMed:15930137, PubMed:22036712, PubMed:23922729). Forms a complex with NHLRC1/malin and HSP70 (PubMed:19036738). Interacts with PPP1R3D; in the presence of NHLC1/malin the interaction leads to ubiquitination and autophagic degradation of PPP1R3D. Interacts (via the phosphatase domain) with MAPT/Tau; the interaction dephosphorylates MAPT (PubMed:19542233). Isoform 1 and isoform 2 interact to form a heterodimeric complex that lacks phosphatase activity (in vitro) (PubMed:18617530). Active phosphatase isoform 7 and isoform 1 interact with each other, but give rise to lower phosphatase activity than isoform 1 or isoform 7 by themselves (in vitro) (PubMed:22036712). Active phosphatase isoform 7 and inactive isoform 2 interact with each other, but give rise to lower phosphatase activity than isoform 7 by itself (in vitro) (PubMed:22036712). Interacts with PRDM8 (PubMed:22961547).18 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113679, 23 interactors
IntActiO95278, 4 interactors
STRINGi9606.ENSP00000356489

Chemistry databases

BindingDBiO95278

Structurei

Secondary structure

1331
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO95278
SMRiO95278
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 124CBM20PROSITE-ProRule annotationAdd BLAST124
Domaini243 – 311Tyrosine-protein phosphataseAdd BLAST69

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni103 – 107Substrate bindingCombined sources1 Publication5
Regioni267 – 272Substrate bindingCombined sources1 Publication6

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi266 – 272Glucan phosphatase signature motif CXAGXGR2 Publications7

Domaini

The CBM20 domain mediates binding to cytoplasmic glycogen and to Lafora polyglucosan bodies.2 Publications

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1716 Eukaryota
COG2453 LUCA
GeneTreeiENSGT00390000010101
HOGENOMiHOG000285975
HOVERGENiHBG051493
KOiK14165
OMAiRKVQYFV
OrthoDBiEOG091G0GBM
PhylomeDBiO95278
TreeFamiTF332841

Family and domain databases

CDDicd05806 CBM20_laforin, 1 hit
Gene3Di2.60.40.10, 1 hit
3.90.190.10, 1 hit
InterProiView protein in InterPro
IPR013784 Carb-bd-like_fold
IPR034831 CBM20_laforin
IPR002044 CBM_fam20
IPR000340 Dual-sp_phosphatase_cat-dom
IPR024950 DUSP
IPR013783 Ig-like_fold
IPR029021 Prot-tyrosine_phosphatase-like
IPR016130 Tyr_Pase_AS
IPR000387 TYR_PHOSPHATASE_dom
IPR020422 TYR_PHOSPHATASE_DUAL_dom
PANTHERiPTHR10159 PTHR10159, 1 hit
PfamiView protein in Pfam
PF00686 CBM_20, 1 hit
PF00782 DSPc, 1 hit
SMARTiView protein in SMART
SM01065 CBM_2, 1 hit
SM00195 DSPc, 1 hit
SUPFAMiSSF49452 SSF49452, 1 hit
SSF52799 SSF52799, 1 hit
PROSITEiView protein in PROSITE
PS51166 CBM20, 1 hit
PS00383 TYR_PHOSPHATASE_1, 1 hit
PS50056 TYR_PHOSPHATASE_2, 1 hit
PS50054 TYR_PHOSPHATASE_DUAL, 1 hit

Sequences (8)i

Sequence statusi: Complete.

This entry describes 8 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket
Isoform 1 (identifier: O95278-1) [UniParc]FASTAAdd to basket
Also known as: A, LDH11 Publication, Laf3311 Publication

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MRFRFGVVVP PAVAGARPEL LVVGSRPELG RWEPRGAVRL RPAGTAAGDG
60 70 80 90 100
ALALQEPGLW LGEVELAAEE AAQDGAEPGR VDTFWYKFLK REPGGELSWE
110 120 130 140 150
GNGPHHDRCC TYNENNLVDG VYCLPIGHWI EATGHTNEMK HTTDFYFNIA
160 170 180 190 200
GHQAMHYSRI LPNIWLGSCP RQVEHVTIKL KHELGITAVM NFQTEWDIVQ
210 220 230 240 250
NSSGCNRYPE PMTPDTMIKL YREEGLAYIW MPTPDMSTEG RVQMLPQAVC
260 270 280 290 300
LLHALLEKGH IVYVHCNAGV GRSTAAVCGW LQYVMGWNLR KVQYFLMAKR
310 320 330
PAVYIDEEAL ARAQEDFFQK FGKVRSSVCS L
Length:331
Mass (Da):37,158
Last modified:May 1, 2000 - v2
Checksum:iDD79F917262AB458
GO
Isoform 2 (identifier: O95278-2) [UniParc]FASTAAdd to basket
Also known as: B, C-terISO, Laf3171 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     310-320: LARAQEDFFQK → ASQDTFPL
     321-331: Missing.

Note: Produced by alternative splicing.
Show »
Length:317
Mass (Da):35,519
Checksum:i5646A039398AC24D
GO
Isoform 4 (identifier: O95278-4) [UniParc]FASTAAdd to basket
Also known as: Laf1521 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     102-199: NGPHHDRCCT...MNFQTEWDIV → IASRRLPPAQ...VPAHSPGDLG
     200-331: Missing.

Note: Produced by alternative splicing. May be due to an intron retention.
Show »
Length:152
Mass (Da):15,804
Checksum:i60CD9293F2267EC4
GO
Isoform 5 (identifier: O95278-5) [UniParc]FASTAAdd to basket
Also known as: Laf2241 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     160-293: Missing.
     294-331: YFLMAKRPAV...GKVRSSVCSL → PSTDAAPGGV...PHGQEAGCLH

Note: Produced by alternative splicing.
Show »
Length:224
Mass (Da):24,134
Checksum:i66ECE43870086B2A
GO
Isoform 6 (identifier: O95278-6) [UniParc]FASTAAdd to basket
Also known as: Laf881 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-243: Missing.

Note: Produced by alternative initiation at Met-244 of isoform 1. Transcript amplified but protein not detected.1 Publication
Show »
Length:88
Mass (Da):9,933
Checksum:iD28FAB18CC285D07
GO
Isoform 7 (identifier: O95278-7) [UniParc]FASTAAdd to basket
Also known as: Laf1771 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-159: MRFRFGVVVP...AGHQAMHYSR → MIFNK

Note: Produced by alternative splicing. Active phosphatase.1 Publication
Show »
Length:177
Mass (Da):20,256
Checksum:i5AE29B26B72E7BF7
GO
Isoform 8 (identifier: O95278-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-138: Missing.

Note: Produced by alternative splicing. No experimental confirmation available.
Show »
Length:193
Mass (Da):22,160
Checksum:i3DC9436A9885B915
GO
Isoform 9 (identifier: B3EWF7-1) [UniParc]FASTAAdd to basket
Also known as: POCR1 Publication
The sequence of this isoform can be found in the external entry B3EWF7.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Produced by alternative initiation. Arises due to the use of an alternative initiation codon in exon 1 out of frame with isoform 1 and results in a completely different isoform.
Length:344
Mass (Da):35,169
GO

Sequence cautioni

The sequence AAO15523 differs from that shown. Probable cloning artifact.Curated
The sequence BAG51107 differs from that shown. Reason: Frameshift at position 223.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti193Q → K in AAH70047 (PubMed:15489334).Curated1
Sequence conflicti248A → P in AAO15523 (Ref. 4) Curated1
Sequence conflicti258K → E in BAG61454 (PubMed:14702039).Curated1
Sequence conflicti294Y → H in BAG61454 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01946525S → P in EPM2; atypical form; does not affect glycogen binding. 2 Publications1
Natural variantiVAR_01946628E → K in EPM2; does not affect glycogen binding. 1 Publication1
Natural variantiVAR_01946732W → G in EPM2; impairs protein stability; affects phosphatase activity; abolishes glycogen binding; abolishes phosphatase activity with insoluble glucan; disrupts the interaction with PPP1R3C. 6 PublicationsCorresponds to variant dbSNP:rs104893955EnsemblClinVar.1
Natural variantiVAR_01946846A → P Does not affect glycogen binding. 3 PublicationsCorresponds to variant dbSNP:rs374338349EnsemblClinVar.1
Natural variantiVAR_01946984F → L in EPM2; affects phosphatase activity and glycogen binding; disrupts the interaction with PPP1R3C. 2 PublicationsCorresponds to variant dbSNP:rs1362231306Ensembl.1
Natural variantiVAR_01947088F → L in EPM2; does not affect glycogen binding. 1 Publication1
Natural variantiVAR_01947191R → P in EPM2; atypical form; learning difficuties with childhood-onset. 2 Publications1
Natural variantiVAR_019472108R → C in EPM2; loss of phosphatase activity; reduced self-interaction capacity; disrupts the interaction with PPP1R3C. 3 PublicationsCorresponds to variant dbSNP:rs137852915EnsemblClinVar.1
Natural variantiVAR_019473114E → D1 Publication1
Natural variantiVAR_046383140K → N in EPM2. 1 Publication1
Natural variantiVAR_046384148N → Y in EPM2. 1 Publication1
Natural variantiVAR_019474171R → H in EPM2; results in ubiquitin-positive perinuclear aggregates; no effect on glycogen binding; abolishes phosphatase activity; may affect proper folding. 5 PublicationsCorresponds to variant dbSNP:rs137852916EnsemblClinVar.1
Natural variantiVAR_019475187T → A in EPM2; abolishes interaction with NHLRC1. 1 Publication1
Natural variantiVAR_019476194T → I in EPM2; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; reduced self-interaction capacity; abolishes interaction with NHLRC1, PPP1R3C and PRKAA2; no effect on phosphorylation of protein. 3 PublicationsCorresponds to variant dbSNP:rs375544596Ensembl.1
Natural variantiVAR_046385210E → K in EPM2. 1 Publication1
Natural variantiVAR_019477240G → S in EPM2; impaired phosphatase activity; does not affect glycogen binding; disrupts the interaction with PPP1R3C. 3 Publications1
Natural variantiVAR_019478279G → S in EPM2; results in ubiquitin-positive perinuclear aggregates; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 5 PublicationsCorresponds to variant dbSNP:rs137852917EnsemblClinVar.1
Natural variantiVAR_019479293Q → L in EPM2; results in ubiquitin-positive perinuclear aggregates; may affect proper folding; loss of phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 4 PublicationsCorresponds to variant dbSNP:rs796052427EnsemblClinVar.1
Natural variantiVAR_019480294Y → N in EPM2; results in ubiquitin-positive perinuclear aggregates; impairs phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 4 Publications1
Natural variantiVAR_019481301P → L in EPM2; impairs protein stability; impairs phosphatase activity; affects glycogen binding; disrupts the interaction with PPP1R3C. 3 PublicationsCorresponds to variant dbSNP:rs796052428Ensembl.1
Natural variantiVAR_046386310L → W in EPM2; causes location of isoform 1 at cytoplasmic punctae; does not affect homodimerization of isoform 1 but prevents heterodimerization of isoform 1 and isoform 2. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0424941 – 243Missing in isoform 6. 1 PublicationAdd BLAST243
Alternative sequenceiVSP_0424951 – 159MRFRF…MHYSR → MIFNK in isoform 7. 1 PublicationAdd BLAST159
Alternative sequenceiVSP_0424931 – 138Missing in isoform 8. 2 PublicationsAdd BLAST138
Alternative sequenceiVSP_011015102 – 199NGPHH…EWDIV → IASRRLPPAQSGSSGPHPQP GPRPRAGPAGPGGARPGLFA RVPAHSPGDLG in isoform 4. 1 PublicationAdd BLAST98
Alternative sequenceiVSP_042496160 – 293Missing in isoform 5. CuratedAdd BLAST134
Alternative sequenceiVSP_011016200 – 331Missing in isoform 4. 1 PublicationAdd BLAST132
Alternative sequenceiVSP_042497294 – 331YFLMA…SVCSL → PSTDAAPGGVPAACAAGEGT HRVRALQRWGGPLHRGCLRL APVCDGLESEEGAVFPHGQE AGCLH in isoform 5. CuratedAdd BLAST38
Alternative sequenceiVSP_011017310 – 320LARAQEDFFQK → ASQDTFPL in isoform 2. 2 PublicationsAdd BLAST11
Alternative sequenceiVSP_011018321 – 331Missing in isoform 2. 2 PublicationsAdd BLAST11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF084535 mRNA Translation: AAC83347.2
AF284580 mRNA Translation: AAG18377.1
AF454491 mRNA Translation: AAO15523.1 Sequence problems.
AF454492 mRNA Translation: AAO15524.1
AF454493 mRNA Translation: AAO15525.1
AF454494 mRNA Translation: AAO15526.1
AK022721 mRNA Translation: BAG51107.1 Frameshift.
AK299497 mRNA Translation: BAG61454.1
AL023806 Genomic DNA No translation available.
AL365193 Genomic DNA No translation available.
CH471051 Genomic DNA Translation: EAW47844.1
BC005286 mRNA Translation: AAH05286.1
BC070047 mRNA Translation: AAH70047.1
AJ130763 mRNA Translation: CAA10199.1
AJ130764 mRNA Translation: CAA10200.1
CCDSiCCDS5206.1 [O95278-1]
CCDS87452.1 [O95278-8]
CCDS87453.1 [O95278-5]
CCDS87454.1 [O95278-2]
RefSeqiNP_001018051.1, NM_001018041.1 [O95278-2]
NP_005661.1, NM_005670.3 [O95278-1]
XP_006715627.1, XM_006715564.3
XP_011534418.1, XM_011536116.1 [O95278-8]
XP_016866789.1, XM_017011300.1
XP_016866790.1, XM_017011301.1 [O95278-7]
XP_016866791.1, XM_017011302.1 [O95278-7]
UniGeneiHs.486696

Genome annotation databases

EnsembliENST00000367519; ENSP00000356489; ENSG00000112425 [O95278-1]
ENST00000435470; ENSP00000405913; ENSG00000112425 [O95278-2]
ENST00000611340; ENSP00000480268; ENSG00000112425 [O95278-8]
ENST00000618445; ENSP00000480339; ENSG00000112425 [O95278-2]
ENST00000638262; ENSP00000492876; ENSG00000112425 [O95278-5]
ENST00000638778; ENSP00000491353; ENSG00000112425 [O95278-8]
ENST00000638783; ENSP00000491338; ENSG00000112425 [O95278-8]
ENST00000639423; ENSP00000492701; ENSG00000112425 [O95278-8]
ENST00000639465; ENSP00000491180; ENSG00000112425 [O95278-8]
GeneIDi7957
KEGGihsa:7957
UCSCiuc003qkw.4 human [O95278-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

The Lafora progressive myoclonus epilepsy mutation and polymorphism database

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF084535 mRNA Translation: AAC83347.2
AF284580 mRNA Translation: AAG18377.1
AF454491 mRNA Translation: AAO15523.1 Sequence problems.
AF454492 mRNA Translation: AAO15524.1
AF454493 mRNA Translation: AAO15525.1
AF454494 mRNA Translation: AAO15526.1
AK022721 mRNA Translation: BAG51107.1 Frameshift.
AK299497 mRNA Translation: BAG61454.1
AL023806 Genomic DNA No translation available.
AL365193 Genomic DNA No translation available.
CH471051 Genomic DNA Translation: EAW47844.1
BC005286 mRNA Translation: AAH05286.1
BC070047 mRNA Translation: AAH70047.1
AJ130763 mRNA Translation: CAA10199.1
AJ130764 mRNA Translation: CAA10200.1
CCDSiCCDS5206.1 [O95278-1]
CCDS87452.1 [O95278-8]
CCDS87453.1 [O95278-5]
CCDS87454.1 [O95278-2]
RefSeqiNP_001018051.1, NM_001018041.1 [O95278-2]
NP_005661.1, NM_005670.3 [O95278-1]
XP_006715627.1, XM_006715564.3
XP_011534418.1, XM_011536116.1 [O95278-8]
XP_016866789.1, XM_017011300.1
XP_016866790.1, XM_017011301.1 [O95278-7]
XP_016866791.1, XM_017011302.1 [O95278-7]
UniGeneiHs.486696

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4R30X-ray2.30A/B/C/D148-331[»]
4RKKX-ray2.40A/C1-329[»]
ProteinModelPortaliO95278
SMRiO95278
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113679, 23 interactors
IntActiO95278, 4 interactors
STRINGi9606.ENSP00000356489

Chemistry databases

BindingDBiO95278
ChEMBLiCHEMBL2311242

Protein family/group databases

CAZyiCBM20 Carbohydrate-Binding Module Family 20

PTM databases

DEPODiO95278
iPTMnetiO95278
PhosphoSitePlusiO95278

Polymorphism and mutation databases

BioMutaiRNF213

Proteomic databases

EPDiO95278
PaxDbiO95278
PeptideAtlasiO95278
PRIDEiO95278
ProteomicsDBi50779
50780 [O95278-2]
50782 [O95278-4]
50783 [O95278-5]
50784 [O95278-6]
50785 [O95278-7]
50786 [O95278-8]

Protocols and materials databases

DNASUi7957
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000367519; ENSP00000356489; ENSG00000112425 [O95278-1]
ENST00000435470; ENSP00000405913; ENSG00000112425 [O95278-2]
ENST00000611340; ENSP00000480268; ENSG00000112425 [O95278-8]
ENST00000618445; ENSP00000480339; ENSG00000112425 [O95278-2]
ENST00000638262; ENSP00000492876; ENSG00000112425 [O95278-5]
ENST00000638778; ENSP00000491353; ENSG00000112425 [O95278-8]
ENST00000638783; ENSP00000491338; ENSG00000112425 [O95278-8]
ENST00000639423; ENSP00000492701; ENSG00000112425 [O95278-8]
ENST00000639465; ENSP00000491180; ENSG00000112425 [O95278-8]
GeneIDi7957
KEGGihsa:7957
UCSCiuc003qkw.4 human [O95278-1]

Organism-specific databases

CTDi7957
DisGeNETi7957
EuPathDBiHostDB:ENSG00000112425.13
GeneCardsiEPM2A
GeneReviewsiEPM2A
HGNCiHGNC:3413 EPM2A
HPAiHPA053643
HPA055468
MalaCardsiEPM2A
MIMi254780 phenotype
607566 gene
neXtProtiNX_O95278
OpenTargetsiENSG00000112425
Orphaneti501 Lafora disease
PharmGKBiPA27832
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1716 Eukaryota
COG2453 LUCA
GeneTreeiENSGT00390000010101
HOGENOMiHOG000285975
HOVERGENiHBG051493
KOiK14165
OMAiRKVQYFV
OrthoDBiEOG091G0GBM
PhylomeDBiO95278
TreeFamiTF332841

Enzyme and pathway databases

BRENDAi3.1.3.16 2681
ReactomeiR-HSA-3322077 Glycogen synthesis
R-HSA-3785653 Myoclonic epilepsy of Lafora
SIGNORiO95278

Miscellaneous databases

ChiTaRSiEPM2A human
GenomeRNAii7957
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000112425 Expressed in 222 organ(s), highest expression level in skeletal muscle tissue of rectus abdominis
CleanExiHS_EPM2A
ExpressionAtlasiO95278 baseline and differential
GenevisibleiO95278 HS

Family and domain databases

CDDicd05806 CBM20_laforin, 1 hit
Gene3Di2.60.40.10, 1 hit
3.90.190.10, 1 hit
InterProiView protein in InterPro
IPR013784 Carb-bd-like_fold
IPR034831 CBM20_laforin
IPR002044 CBM_fam20
IPR000340 Dual-sp_phosphatase_cat-dom
IPR024950 DUSP
IPR013783 Ig-like_fold
IPR029021 Prot-tyrosine_phosphatase-like
IPR016130 Tyr_Pase_AS
IPR000387 TYR_PHOSPHATASE_dom
IPR020422 TYR_PHOSPHATASE_DUAL_dom
PANTHERiPTHR10159 PTHR10159, 1 hit
PfamiView protein in Pfam
PF00686 CBM_20, 1 hit
PF00782 DSPc, 1 hit
SMARTiView protein in SMART
SM01065 CBM_2, 1 hit
SM00195 DSPc, 1 hit
SUPFAMiSSF49452 SSF49452, 1 hit
SSF52799 SSF52799, 1 hit
PROSITEiView protein in PROSITE
PS51166 CBM20, 1 hit
PS00383 TYR_PHOSPHATASE_1, 1 hit
PS50056 TYR_PHOSPHATASE_2, 1 hit
PS50054 TYR_PHOSPHATASE_DUAL, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiEPM2A_HUMAN
AccessioniPrimary (citable) accession number: O95278
Secondary accession number(s): B3KMU5
, B4DRZ2, O95483, Q5T3F5, Q6IS15, Q8IU96, Q8IX24, Q8IX25, Q9BS66, Q9UEN2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: May 1, 2000
Last modified: November 7, 2018
This is version 161 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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